Retroviruses are important agents in the etiology of cancers and other human diseases. Human T-lymphotrophic virus type I (HTLV-I) causes adult T-cell leukemia as shown by epidemiologic and experimental data. Based on ATL incidence data from a population registry, early life exposure is critical for subsequent disease occurrence. Infective dermatitis was recognized as an HTLV-I associated syndrome with pre-leukemic potential. Spontaneous lymphocyte proliferation of peripheral blood cells from HTLV positive individuals may provide new insights into the process of leukemogenesis. American Indian populations in Northern, Central and South America may be the natural reservoir for HTLV-II infection, a virus previously associated with parenteral drug abuse. No specific disease association with HTLV-II, has been identified. Studies of HIV transmission have provided new insights of relevance to vaccine development by the finding that maternal-to-child transmission is prevented by high affinity antibodies to HIV in the mother's serum. The major cofactor associated with more rapid progression to clinical AIDS is older age, while there are no major differences by risk group and calendar time of infection. Intermediate markers such as CD4 count decline more rapidly in older HIV-infected persons and have a more ominous prognostic significance compared to those in younger persons. Prophylactic therapy appears to be postponing clinical AIDS in significant numbers of severely immunosuppressed individuals. With prolonged survival, an increasing proportion of HIV coinfected persons will develop lymphoma as their initial manifestation. DNA tumor viruses are possible cofactors in HIV-1 related malignancy, and the newly discovered human herpesvirus 6 may have oncogenic potential.